Prostate cancer is the second leading cause of cancer death in American men, behind only lung cancer. In 2012, it is estimated that about 241,740 new cases of prostate cancer will be diagnosed and about 28,170 men will die of prostate cancer. Treatment options currently available for prostate cancer patients include surgery, radiation, hormonal therapy and chemotherapy. In addition, patients with castration-resistant prostate cancer with bone metastases are often treated with bisphosphonates to prevent skeletal-related events.
As a bone dominant disease, changes in prostate cancer metastases are difficult to assess using conventional imaging modalities,1,2 and only part of the treatment effect is reflected in serum prostate specific antigen (PSA) changes.3 
Src and other Src family kinases (SFKs) are involved in activating survival, invasion and migration pathways in prostate cancer and may contribute to the initial transition from a castration-sensitive to castration-resistant state by activating the androgen receptor (AR) in an androgen-independent manner (5-14). The expression and activity of the Src kinase is high in osteoclasts and has been reported to be crucial for osteoclast maturation and bone resorptive activity (5, 15-17). SFK activity is increased in castrate resistant prostate cancer (CRPC) and predicts for shorter overall survival (18). Inhibition of Src signaling decreased proliferation, invasion and migration of prostate cancer cell lines in vitro. There is also evidence for direct interaction of Src with steroid receptors in a steroid ligand-independent manner (5). Other dasatinib-sensitive kinases have been implicated in the pathogenesis of metastatic prostate cancer as well; these include EphA2 (19, 20), Lyn (21), PDGFR (22, 23) and c-fms, a key regulator of osteoclastogenesis (24).
Dasatinib is an oral tyrosine kinase inhibitor that inhibits BCR-ABL, Abl, Src and other Src-family kinases (Lck, Hck, Yes, Fgr, Lyn and Fyn), EphA2, c-KIT, PDGFR-α and -β, and the macrophage colony-stimulating factor (M-CSF) receptor, c-fms. Dasatinib is currently approved for the treatment of patients with imatinib-resistant or -intolerant chronic myelogenous leukemia (CML) or Ph+ acute lymphoblastic leukemia (ALL) (1). A Phase III dose optimization study showed that in patients with chronic phase CML, 100 mg once-daily dasatinib improves the safety profile, particularly decreasing pleural effusion and thrombocytopenia, while maintaining efficacy compared with the previously recommended dose of 70 mg twice-daily (1-4).
Evidence from preclinical models of prostate cancer suggests that dasatinib has anti-proliferative and anti-osteoclastic activity and supports the potential of dasatinib as a targeted therapy for prostate cancer (5). Dasatinib also inhibits cell adhesion, migration and invasion in in vitro model systems of prostate carcinoma (25). In orthotopic nude mouse models, dasatinib treatment effectively inhibited both tumor growth and development of lymph node metastases in both castration-sensitive and castration-resistant tumors.
A recent phase II clinical study (Yu et al.) showed dasatinib to be a promising agent for addressing bone morbidity as well as metastasis in chemotherapy-naïve patients with metastatic CRPC, paving the way for a phase III trial evaluating the effects of the addition of dasatinib to docetaxel on overall survival and skeletal-related events.
Prostate cancer is a heterogeneous disease consisting of various forms that differ in their risk of recurrence and response to therapy; the likelihood of treatment success of prostate cancer depends on accurate assessment of disease subtype. Therefore, the need exists for inexpensive and accurate diagnostic methods.
The need for molecular biomarkers from a sample obtained repeatedly and with little inconvenience to the patient and capable of predicting overall survival and responsiveness to treatment has recently focused on the technological advances in circulating tumor cell (CTC) detection, isolation, and capture. First described in 1869,4 CTC may be obtained from phlebotomy samples in a routine clinical practice setting. Initial studies of CTC in prostate cancer focused on detection of tumor cells using a reverse-transcription polymerase chain reaction (RT-PCR) based assay for the messenger RNA (mRNA) for PSA, also called kallikrein-related peptidase 3 (KLK3), in the mononuclear cell fraction of the blood that are presumed to be from CTC.5 To improve RT-PCR detection in peripheral blood, additional genes, highly expressed in tumor tissue and not expressed in peripheral blood nucleated cells (PBMC), have been studied as biomarkers to detect minimal residual or recurrent disease, such as prostate-specific membrane antigen, or markers of epithelial mesenchymal transition, or stem-cell origin.10,11 
Thus, there is a critical unmet need in prostate cancer drug development and treatment for outcome measures that reflect clinical benefit.